Millions of Years of Evolution Preserved: A Comprehensive Catalog of the Processed Pseudogenes in the Human Genome

Abstract

Processed pseudogenes were created by reverse-transcription of mRNAs; they provide snapshots of ancient genes existing millions of years ago in the genome. To find them in the present-day human, we developed a pipeline using features such as intron-absence, frame-disruption, polyadenylation, and truncation. This has enabled us to identify in recent genome drafts ∼8000 processed pseudogenes (distributed from http://pseudogene.org). Overall, processed pseudogenes are very similar to their closest corresponding human gene, being 94% complete in coding regions, with sequence similarity of 75% for amino acids and 86% for nucleotides. Their chromosomal distribution appears random and dispersed, with the numbers on chromosomes proportional to length, suggesting sustained "bombardment" over evolution. However, it does vary with GC-content: Processed pseudogenes occur mostly in intermediate GC-content regions. This is similar to Alus but contrasts with functional genes and L1-repeats. Pseudogenes, moreover, have age profiles similar to Alus. The number of pseudogenes associated with a given gene follows a power-law relationship, with a few genes giving rise to many pseudogenes and most giving rise to few. The prevalence of processed pseudogenes agrees well with germ-line gene expression. Highly expressed ribosomal proteins account for ∼20% of the total. Other notables include cyclophilin-A, keratin, GAPDH, and cytochrome c.

Why rodent pseudogenes refuse to retire

“…Irrespective of whether you have a taste for wine or not, your genome will harbor at least one alcohol dehydrogenase homolog that does not encode any dehydrogenase, but is instead a pseudogene [1]. In fact, scattered in our genomes there are as many as 20,000 pseudogenes, two-fifths having been created by RNA-based duplication [2,3]. Given that by definition these pseudogenes do not produce competent proteins, they might be expected to accept the evolutionary fate of shrinking by negative selection, which would ultimately result in a complete disappearance from the genome [4].…”

A genome-wide CNV association study on panic disorder in a Japanese population

“…Pseudogenes and non-coding RNAs (including microRNAs and small nucleolar RNAs (snoRNAs)) were sought in the union region using existing databases (Pseudogene.org, 33 miRBase, 34 snoRNABase 35 and NONCODE 36 ), as Salmena et al 37 recently emphasized their important roles in pathological conditions. Although no miRNAs or snoRNAs were found, 50 pseudogenes (listed in Supplementary Table 2) and 241 PIWI-interacting RNAs (piRNAs; shown in Supplementary Figure 2) were detected in the union region.…”

L’apophénie d’ENCODE ou Pangloss examine le génome humain

“…En fait, cet ADN n'est pas si noir que ça, car il est depuis longtemps établi qu'il est pour l'essentiel composé de fragments de transposons, plus ou moins anciens et donc parfois très difficiles à identifier [21], et de pseudogènes qui ne sont pas transcrits en ARN utiles au fonctionnement de l'organisme [22]. Il y a en outre une bonne dose de séquences de plus ou moins grandes tailles qui sont plus ou moins répétées, les microsatellites, minisatellites et autres satellites.…”